在加州大学伯克力分校进行的两项新研究中，研究人员发现基因分布在不同种类中的情况异常混乱，而且原始生物之间分享基因的情况更明显，甚至往往共享的不只是几个基因，而是整个基因群。这两项研究的论文分别发表在3月7日的《自然》杂志和近期的《PNAS》上。
基因在不同物种间流动的这种现象就是所谓的基因水平转移（横向移动）。之前的研究显示，在细菌中经常可以观察到这种现象促使致病细菌可以将抗药性基因与其它细菌交换共享，从而导致细菌抗药性的快速蔓延。
此前，研究人员发现二种不同种类的植物也会分享基因，但是却不清楚这种现象有多普遍以及是如何发生的。
发表在PNAS的研究显示，加州大学伯克力分校和劳伦斯伯克力国家实验室(LBNL)的研究人员分析了超过8,000种不同的基因家族，这些基因编码的蛋白质可代表所有生物中数以百万计的蛋白质。研究人员希望通过这项浩大的分析研究来评估基因水平转移的发生率。
他们发现一半以上最原始的有机生物——古菌(Archaea)，有一个以上的蛋白质基因是通过基因水平转移途径获得的；而细菌通过这种途径获得基因的百分率则为30％到50％；真核生物则只有10％的几率。
第二项研究发表于3月7日Nature网络版上。这项研究中，研究人员发现了生活在加州酸性红泥土中的二种细菌分享了一大群基因。这些基因编码的蛋白质具有合作的功能，因此研究人员认为，这种特性可以帮助细菌适应同样类型的新环境。此外，这项研究也是第一次观察到一大群基因发生基因水平转移的现象。
部分英文全文：
Published online before print March 7, 2007, 10.1073/pnas.0611557104
PNAS | March 13, 2007 | vol. 104 | no. 11 | 4489-4494
Global extent of horizontal gene transfer
In-Geol Choi*, and Sung-Hou Kim
Physical Biosciences Division, Lawrence Berkeley National Laboratory and Department of Chemistry, University of California, Berkeley, CA 94720
Contributed by Sung-Hou Kim, December 28, 2006 (received for review July 1, 2006)
Abstract
Horizontal gene transfer (HGT) is thought to play an important role in the evolution of species and innovation of genomes. There have been many convincing evidences for HGT for specific genes or gene families, but there has been no estimate of the global extent of HGT. Here, we present a method of identifying HGT events within a given protein family and estimate the global extent of HGT in all curated protein domain families (8,000) listed in the Pfam database. The results suggest four conclusions: (i) for all protein domain families in Pfam, the fixation of genes horizontally transferred is not a rampant phenomenon between organisms with substantial phylogenetic separations (1.1–9.7% of Pfam families surveyed at three taxonomic ranges studied show indication of HGT); (ii) however, at the level of domains, >50% of Archaea have one or more protein domains acquired by HGT, and nearly 30–50% of Bacteria did the same when examined at three taxonomic ranges. But, the equivalent value for Eukarya is <10%; (iii) HGT will have very little impact in the construction of organism phylogeny, when the construction methods use whole genomes, large numbers of common genes, or SSU rRNAs; and (iv) there appears to be no strong preference of HGT for protein families of particular cellular or molecular functions.
protein domain family | protein sequence family | lateral gene transfer
One of the new important concepts that emerged from a large number of genomic sequences in the last decade is that of horizontal gene transfer (HGT): gene transfer among organisms of different species. HGT has been found to have occurred in all three domains: Archaea, Bacteria, and Eukarya. The concept of HGT has been evoked to interpret various evolutionary processes ranging from speciation and the adaptation of organisms to uncertainties in phylogenetic inference of the tree of life (1–9). Although HGT has been regarded as a driving force in the innovation and evolution of genomes, especially in prokaryotes, its extent and impact on the evolutionary process and phylogeny of organisms or species remains controversial (8–10).
There have been several methods developed to detect HGT, including (i) difference between gene trees derived from a limited number of gene families and the reference trees such as the small-subunit ribosomal RNA (SSU rRNA) tree (11–13) or whole genome tree (14); (ii) unexpectedly high sequence similarity of a gene from two distant genomes compared with those among homologous genes in closely related genomes (15); and (iii) unusual nucleotide composition or codon usages of a gene compared with the rest of the genes within a genome (16, 17). Many factors affect the detection of HGT, such as lineage-specific gene loss (18, 19), unequal rates of base substitution (1), loss of signal due to amelioration processes (16), and others (1, 15).
It has been suggested that HGT may have been "rampant" in primitive genomes (6, 20), but, for modern organisms, it may not be a dominant factor in speciation, because HGT has less effect on overall genome phylogeny (10, 21).
There have been many convincing evidences for HGT for specific genes or gene families, but there has been no estimate of the global extent of HGT in terms of protein domains. Here, we present a statistical method to identify the member(s) in a protein family that may have joined the family by HGT events and examine the global extent of HGT events for all protein domain families of known curated sequences at various ranges of taxonomic levels.
A protein (sequence) domain is a functionally independent unit in protein sequence. The gene coding for it often behaves like a modular genetic element that transfers within or between genomes, sometimes forming a new gene coding for a multiple domain protein (22–24). Because the fixation of a new gene during evolution depends mostly on its advantage for survival, we focus on HGT of the genetic module coding for the sequence domains, rather than the entire genes. At present, there are 1.2 million curated protein domain sequences from three domains of life (Archaea, Bacteria, and Eukarya) in the Pfam (release 16.0) (25).
英文全文链接：http://www.pnas.org/cgi/content/full/104/11/4489
Nature advance online publication 7 March 2007 | doi:10.1038/nature05690; Received 7 November 2006; Accepted 20 February 2007; Published online 7 March 2007
Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia
Charles G. Mullighan1,6, Salil Goorha1,6, Ina Radtke1, Christopher B. Miller1, Elaine Coustan-Smith2, James D. Dalton1, Kevin Girtman1, Susan Mathew1,7, Jing Ma5, Stanley B. Pounds3, Xiaoping Su5, Ching-Hon Pui2, Mary V. Relling4, William E. Evans4, Sheila A. Shurtleff1 and James R. Downing1
Departments of Pathology,
Oncology,
Biostatistics,
Pharmaceutical Sciences, and the
Hartwell Center for Bioinformatics and Biotechnology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA
These authors contributed equally to this work.
Present address: The Department of Pathology & Laboratory Medicine, New York Presbyterian Hospital, Cornell Campus, 525 East 68th Street, F511, New York, New York 10021, USA.
Correspondence to: James R. Downing1 Correspondence and requests for materials should be addressed to J.R.D. (Email: james.downing@stjude.org).
Abstract
Chromosomal aberrations are a hallmark of acute lymphoblastic leukaemia (ALL) but alone fail to induce leukaemia. To identify cooperating oncogenic lesions, we performed a genome-wide analysis of leukaemic cells from 242 paediatric ALL patients using high-resolution, single-nucleotide polymorphism arrays and genomic DNA sequencing. Our analyses revealed deletion, amplification, point mutation and structural rearrangement in genes encoding principal regulators of B lymphocyte development and differentiation in 40% of B-progenitor ALL cases. The PAX5 gene was the most frequent target of somatic mutation, being altered in 31.7% of cases. The identified PAX5 mutations resulted in reduced levels of PAX5 protein or the generation of hypomorphic alleles. Deletions were also detected in TCF3 (also known as E2A), EBF1, LEF1, IKZF1 (IKAROS) and IKZF3 (AIOLOS). These findings suggest that direct disruption of pathways controlling B-cell development and differentiation contributes to B-progenitor ALL pathogenesis. Moreover, these data demonstrate the power of high-resolution, genome-wide approaches to identify new molecular lesions in cancer.
